This invention provides a safer and more effective treatment for non-intracavitary undesirable tissue masses, especially bone cancer and soft tissue tumors. The method involves the direct administration of a therapeutically-effective dose of a formulated radioisotope composition nearby or directly into the tissue mass. Small volumes of the composition are used. Administration of the dose for bone cancer may be done through a hole or multiple holes created in the bone using a miniature drill. Delivery of the dose directly into a tumor may be accomplished using a microsyringe or a miniature pump capable of accurately delivering microliter amounts of material.

DESCRIPTION (provided by applicant): Bone-seeking radiopharmaceuticals are used extensively for bone pain palliation and have shown promise for treating bone metastases. They typically combine a radioactive metal such as samarium-153 with a chelator. The chelator part of the molecule is taken up by growing bone and carries the radioactive payload along with it. Approximately 50% of the radioactivity in the radiopharmaceutical concentrates in bone. The radioactive atoms that are taken up by the bone irradiate the adjacent tumor and micrometastases. This radiation absorbed dose produces the therapeutic benefit. Two bone-seeking radiopharmaceuticals have been investigated for treating bone tumors and micrometastases and have shown promising clinical results but they have proven to be either too weak or too strong. One has an inefficient chelator that limits how much radioactivity may be delivered to the bone. The other has a radionuclide that is so strong that it causes intolerable side effects. We are developing the radiopharmaceutical, samarium-153-DOTMP (CycloSamTM), for the treatment of bone metastases. Compared to the two compounds that have already been tried, CycloSam combines the better radionuclide, samarium-153, with the better phosphonic acid chelator, DOTMP. We anticipate that CycloSam will be able to deliver the prescribed radiation absorbed dose to bone tumors and micrometastases while avoiding intolerable irradiation of normal tissues. Phase I of our work will demonstrate that 1. CycloSam may be used at whatever strength is needed to achieve the prescribed treatment, 2. CycloSam has the requisite biological distribution properties to enable it to deliver high radiation to the skeleton and low radiation to the rest of the body, and 3. CycloSam concentrates in bone tumors even more than in normal bones. In this Phase I proposal, we will measure the time- and concentration-dependent biodistribution properties of CycloSam and theoretically assess its curative capability in rats in Aims 1 and 2. In Aim 3, we will administer CycloSam to dogs with osteosarcomas to demonstrate its concentration in skeletal lesions. In Phase II, we will perform dose escalation, efficacy and late effects studies in dogs and toxicology studies. In Phase III we will conduct clinical trials. PUBLIC HEALTH RELEVANCE: Bone metastases have been treated by radioactive drugs, or radiopharmaceuticals. Thus far, their effects have been primarily palliative. We are developing the radiopharmaceutical, CycloSamTM, to act directly upon and resolve metastatic lesions instead of providing only pain palliation.

The radioisotope tin-117m (117mSn) is a theranostic isotope that is suitable for both diagnostic and therapeutic applications. Its low energy gamma rays can be imaged using standard gamma cameras. For therapy its short-range ( & lt;300 micron) conversion electrons minimize damage to healthy tissue. These emissions, along with its 13.6-day half-life, make tin-117m of interest in a variety of biomedical applications, including several in the fields of oncology and cardiology. While tin-117m can be produced through a variety of methods, there are limiting factors that must be addressed in order to facilitate drug development and commercialization efforts. Tin-117m can be produced in large quantities in reactors; however, the low ( & lt;20 Ci/g) specific activity (SA) product is not suitable for many clinical applications. For example in receptor-targeted therapies, where there are a limited number of receptor sites, mid SA ( & gt;100 Ci/g) and/or high SA ( & gt;1,000 Ci/g) material is required. High SA material is available using accelerator-based production methods, but the small number of suitable accelerators limits quantities available to less than a few Ci per week. Expected future commercial demands will likely require tens of Ci per week of mid and high SA material. Meeting the anticipated need can only be realized with the construction of many costly new accelerators or with a new approach for producing mid and high SA material. Our goal in this project is to determine the technical and economic feasibility of producing mid and high SA tin-117m by electromagnetic (EM) mass separation of readily available low SA reactor-produced material. EM mass separation is used in the production of enriched stable isotopes; however, the successful development of an economically viable EM facility for the production of short-lived medical isotopes presents new challenges. Primary issues involve ion source performance and overall process efficiency. Phase I will focus on issues related to ion source and process development. We aim to intensively study ion source performance in order to determine the optimal combination of feedstock material (e.g. metal or chloride) and ion source. In addition, we intend to measure efficiency of key process steps that influence total production yields and economics. Commercial Applications and Other Benefits: Given the excellent nuclear properties of tin-117m and its potential use as a theranostic isotope, the commercial prospects are outstanding. With the development of a technique to produce the desired specific activity levels, these prospects would be realized. The ultimate objective is to develop and deploy a commercially viable Therapeutic Isotope Separator Facility in partnership with stakeholders. This effort would support drug development efforts that could lead to important patient benefits.